The H-2I-gene-controlled T cell-macrophage interactions involved in immunity to Listeria monocytogenes will be monitored in vitro by antigen-specific T cell proliferation and T cell-induced macrophage activation. Work will center on a new assay system permitting the quantitation of antigen-specific H-2I-gene controlled binding of T cells to macrophages. The proposed work will focus on attempts to understand the mechanism by which H-2 genes dictate specific T cell-macrophage binding and to define macrophage functions required to present Listeria antigen to T cells. The rationale will be to dissect the overall antigen presentation event into separate states (e.g., antigen uptake, antigen catabolism, specific T cell binding) and to study pharmacologically the requirements for each event independently. The involvement of Ia molecules and T cells or T cell products in modulating these events will be addressed. In light of a determinant selection theory of antigen presentation, the possible H-2I-associated specificity of antigen catabolism will be examined. The ability to separate H-2-directed clones of specific T cells on macrophage mono layers will be exploited to analyze the multigenic requirements for multiple clonal responses in F1 hybrid mice, and the possible correlation with increased resistance to listeriosis will be tested. The genetic restriction of binding ability at the precursor T cell level will be determined.